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Evidence-based medicine reversing long-held beliefs about transfusions
Richard Spence, MD, examines the current concepts and issues in blood management and finds better outcomes with fewer transfusions.
We are fortunate to have Dr. Spence’s responses to this month’s interview questions. He is chairman of the department of surgery at St. Agnes Healthcare in Baltimore.
Among Dr. Spence’s areas of expertise has been involvement since 1982 in the care of patients without blood transfusion. This interest led to his development of one of the first bloodless medicine and surgery centers in the world.
He is the only surgeon to have been awarded a Transfusion Medicine Academic Award grant from the National Institutes of Health. Just one of his numerous past activities was chairing the committee responsible for the development of surgical transfusion guidelines that were published in American Journal of Surgery in 1995.
Dr. Spence’s responses to my questions have stimulated me to rethink some of my current premises and practices in postop blood management of my patients. Hopefully, you will experience similar benefits from reading this interview.
Douglas W. Jackson, MD
Chief Medical Editor
Douglas W. Jackson, MD: Why do orthopedic surgeons assume blood transfusions of stored packed red blood cells are beneficial?
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Richard Spence, MD: The easy answer is because of the received knowledge passed on by former generations of orthopedic surgeons. Simple logic tells us that anemia is not a normal physiologic state so correcting it with red cell transfusion should be beneficial. Furthermore, increasing circulating red cell mass should improve oxygen delivery to tissues. Unfortunately, a gathering body of evidence points out that the damage done to blood during storage accentuates its risk and minimizes its benefit.
Toxic cytokines in blood induce the systemic inflammatory response syndrome. Several large-scale retrospective studies have shown that transfusion is directly associated with an increased risk of serious postoperative infection in orthopedic surgical patients. This association persists after case mix adjustment and all other co-variables are taken into consideration.
Other information shows us that the depletion of 2,3 DPG in stored blood severely diminishes its ability to deliver oxygen. Supervital microscopic studies after blood transfusion show that capillaries and small vessels are clogged by deformed cells, which leads to deprivation of oxygen to the tissue where it is most needed.
Finally, multiple studies of patients transfused to liberal vs. restrictive triggers show that those who receive less blood do better in terms of avoiding infection and shortening hospital length of stay.
Jackson: What can we learn from animal studies related to postoperative management of blood loss?
Spence: Animal studies have shown that healthy individuals (in this case experimental animals) can survive without any harm in controlled dilution experiments to a hemoglobin level of 3 to 5 g/dL. This coincides with our understanding of the 4 to 1 relationship between the amount of oxygen available for delivery to that needed by tissues. In other words we have four times the amount of oxygen delivered that our body actually needs. Therefore, reducing red cell mass as shown in these animal studies, does not produce significant harm.
Other animal studies have shown the benefit of replacing volume with asanguineous fluid while rapidly addressing any active bleeding. Maintenance of circulating volume, rather than circulating red cell mass, is the key to successful resuscitation in animal models of trauma and blood loss. These animal models have been corroborated by human research.
The benefits of stimulating erythropoiesis using iron and recombinant human erythropoietin have been demonstrated in animal models and in large-scale human studies as well. All of this work should point out to the orthopedic surgeon that avoidance of blood loss, maintenance of volume, and restoration of red cell mass using erythropoietin and iron rather than transfusion are all major components of perioperative blood management.
Jackson: Can we turn to evidence-based medicine for clinical guidelines on blood transfusions?
Spence: The answer to this question is both yes and no. Guidelines for red cell transfusion have been in existence for many years. In 1988, the NIH Consensus Conference published a document listing guidelines that focused on the need to demonstrate clinical evidence to support transfusion. The clinical evidence addressed included cardiac status, pulmonary status or other changes of hemodynamic instability. The guidelines further suggested that the old 10 g/dL of hemoglobin and 30% hematocrit rule for transfusion was no longer valid.
M. ENGLISH/ CUSTOM MEDICAL STOCK PHOTO |
Many hospital transfusion committees have focused strictly on the number and not on the clinical guidelines, thereby achieving some success with hospital-mandated transfusion triggers in the 7 g to 9 g range.
Unfortunately, many transfusions are still based on a hemoglobin level rather than clinical symptoms. Furthermore, orthopedic surgeons may use predetermined algorithms or treatment pathways that include transfusion at a certain level of Hgb/Hct. These may in part be based on requirements for referral to rehabilitation centers after major joint replacement. In fact there is no evidence to support these types of decisions. Evidence existing from large retrospective reviews and randomized retrospective trials support the concept of minimal transfusion and pharmacologic restoration of erythropoiesis rather than transfusion. This evidence also shows that transfusion provides increased risk as noted above.
We are beginning to see publications in the literature of reports emphasizing the hazards of transfusion as compared to the benefits. It is doubtful that there will ever be a major prospective randomized trial of transfusion vs. no transfusion. Until then the best evidence we have will be from well-structured, large reviews of outcome-focused evidence. We can find some of these in reports dealing with Jehovah’s Witnesses as well as others who have not been transfused. The evidence points to better outcomes with less transfusion.
Jackson: Autologous blood is predonated for a large percentage of joint replacements in this country. What are the benefits, risks, utilization and the needs for additional allogeneic blood?
Spence: Autogolous predonation or PAD was one of the first alternatives to the use of allogeneic blood introduced in this country. Multiple reports of PAD have shown that it can reduce the risk of receiving allogeneic blood. Unfortunately, there is a significant downside to this benefit. Autologous blood predonation requires the patient to complete a predonation schedule two to three weeks before surgery. If surgery is cancelled or postponed for any reason, the predonated blood will expire and is no longer useful. Furthermore, patients who predonate are typically anemic upon arrival in the hospital. As a result, several studies have shown that these patients have a tendency to receive not only their own predonated blood but more allogeneic blood.
Autologous blood that is stored ends up with the same storage lesions as allogeneic blood. These lesions diminish the effectiveness of the red cells as oxygen carriers and can produce a systemic inflammatory response syndrome. There is always the risk of human error with substitution of one person’s autologous blood for another’s. This can lead to severe/lethal blood transfusion reactions. Variations in the use of transfusion alternatives such as PAD exist across the country and around the world. These usually are physician-dependent rather than hospital-based. Approximately 45% of predonated autologous blood is never transfused, which is a costly waste.
In our institution we have began a program of replacing PAD with preoperative assessment and intervention using erythropoietin and iron to correct anemia in selected patients. We supplement this with acute normovolemic hemodilution in the operating room as needed. A closer look at the dynamics of blood transfusions in joint replacement patients can lead to significant changes in practice. For example, an orthopedic surgeon may order two units of blood to be typed and crossed for a patient undergoing a total knee arthroplasty. Since most of these procedures are done with a tourniquet, there is little or no bleeding during the surgery, which means there is no need for blood to be transfused at that time. Any bleeding that occurs from the knee joint will do so following the operation. This blood can be collected and reinfused if needed. Postoperative allogeneic blood transfusion is not needed in the asymptomatic post arthroplasty patient. If symptoms do occur they are typically related to hypovolemia that can be corrected with asanguineous fluids. Ordering a type and cross for two units of blood can tie up blood banking personnel and limits the use of two valuable units of blood for 24 hours.
A lesson to be learned from this example is that type and cross before a knee arthroplasty is inappropriate. If the patient is typed and screened, the blood bank can provide allogeneic blood within 45 minutes postoperatively should it be absolutely indicated. A simple realignment of thinking and management such as this can help improve outcomes for all of our patients while reducing blood usage.
